Improvement in Vasoreactivity in Pre-Penile Arteries and Corpus Cavernosum with SG1002 Supplementation in Castrated Mice

Prostate cancer is one of the most diagnosed cancers in men both in the United States and worldwide with numbers only continuing to grow. One of the frontline treatments for prostate cancer is a form of chemical castration called androgen deprivation therapy (ADT). However, ADT has been associated with long term health ramifications including increased risks of cardiovascular disease and erectile dysfunction. Castration induced severe hypogonadism has been extensively researched for its role in endothelial dysregulation and impaired erectile functioning. Castration causes the deterioration of endothelial functioning as well as the induction of pathologic alterations in vascular remodeling. Maintenance of vascular homeostasis and the balance between vasoconstriction and dilation is critical to both vascular health and erectile functioning. Hydrogen sulfide (H 2 S) acts as a vasodilator and plays a role in maintenance of vascular remodeling. The orally active H 2 S donor SG1002 was used in this study and has previously been demonstrated to induce the desired increase in systemic H 2 S. The objective of this study was to investigate the role of testosterone suppression on vasoreactivity of pre-penile arteries and the corpus cavernosum as well as the evaluation antifibrotic protection of erectile function via SG1002 supplementation. We hypothesized that supplementation of SG1002 will provide a protective role in both vascular and erectile function in a castrated model. Young adult male C57Bl6 mice were divided into four cohorts, one cohort that underwent sham castration surgery and three cohorts that underwent castration. The sham (SHAM) and one castrated cohort (CAST) were maintained on standard chow, while two castrated cohorts received SG1002 mixed into their chow at 20 (CLS) or 100 mg/kg/day (CHS) doses over the 5-week intervention. Ex vivo vascular reactivity was assessed via wire myography for the internal iliac (II) and internal pudendal artery (IPA) and strip myography for the corpus cavernosum (CC). Samples were tested in an increasing dose response manner under the presence of various vasoconstrictors including, phenylephrine (PE), U-46619 (U), and electrical field stimulation (EFS) as well as various vasodilatory stimuli including acetylcholine (Ach), sodium nitroprusside (SNP), sodium sulfide (Na 2 S), testosterone (T) and noradrenergic noncholinergic (NANC) nerve stimulation. Castration resulted in significant impairments to relaxation in both pre-penile arteries and CC as seen in the responses to Ach, SNP, T and NANC-mediated relation. Additionally significant increases to contractile responses U and PE were seen following castration. CHS supplementation was able to blunt the decreases in relaxation seen in IPAs in response to T and NANC-mediated relaxation. With the IPAs being the main artery supplying blood to the penis any preservation of vasoreactivity will also provide a beneficial effect to penile blood flow and erectile function. CHS also saw partial preservation to relaxation in response to T in the CC. Additionally, CHS had a significant decrease in contractile response to PE when compared significant increase seen with CAST and CLS. With a balance of vasodilation and constriction being paramount to erectile function the protective effect of SG1002 supplementation on PE-dependent constriction and T-dependent relaxation in the CC may play an additional protective role in erectile function in an androgen deprived state. Castration results in significant impairments in both erectile and pre-penile artery vasoreactivity that was partially protected via supplementation of SG1002. Department of Health, Nutrition and Food Sciences, College of Education, Health, and Human Sciences, Florida State University, Tallahassee, FL, United States This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.